ABSTRACT This program aims to develop a method for banking clinical-grade bone marrow from cadaveric donors that can be deployed nationally to ameliorate shortages, provide bone marrow stockpiles as medical countermeasures for nuclear threats, and support existing research approaches such as delayed immune tolerance induction and transfusion of HIV-resistant stem cells. We will adapt a method designed by our research team for procurement, processing, and banking bone marrow from cadaveric vertebral bodies, which has been shown to produce high yields of hematopoietic stem cells and other bone marrow cells from heart-beating donors. We have successfully transplanted bone marrow from these sources in clinical trials, with no adverse patient reactions. Now we aim to make key modifications to our method for deployment on a large scale, creating a protocol whereby organ procurement organizations can routinely procure vertebral bodies from a large pool of donors and ship them successfully to a centralized facility for processing, banking, and post-cryopreservation preparation for infusion. This will create a large supply of bone marrow that can be used on-demand, off the shelf, complementing existing bone marrow donor registries and cord blood banks. The technical objectives of this Phase 1 feasibility study are to (1) develop a streamlined procurement protocol allowing organ procurement organizations to ship recovered vertebral bodies to a centralized processing facility, (2) test this optimized protocol for procurement from donors after cardiac death (DCDs) and non-organ tissue donors, and (3) develop a protocol for washout of cryoprotectants at a centralized facility before shipment to clinics. In Aim 1, we will optimize and streamline the existing bone marrow collection and processing protocol for donors following brain death (DBDs), testing multiple preservation solutions for procurement and shipment of donor vertebral body bone marrow. In Aim 2, we will validate that the optimized protocol determined in Aim 1 to can be applied to donors following cardiac death (DCD) and non-organ tissue donors to determine the potential total donor pool. In Aim 3, we will optimize post-cryopreservation processing to allow potential shipment of thawed, large cell volume products to clinics after removal of all cryoprotective agents, testing a hollow fiber dialysis/filtration system that prevents loss of cell yield as cryoprotectants are removed. The outcome of these aims will determine the most effective system for procurement, processing and banking of cadaveric bone marrow for clinical use on a large scale.